The Women's Health Initiative is a randomized controlled clinical trial conducted in 40 clinical centers across the United States addressing some of the most common causes of death, disability, and impaired quality of life in postmenopausal women ages 50-79: cardiovascular disease; breast and colon cancer; and osteoporosis. The three components of this disease prevention trial are: (1) hormone replacement therapy with a primary outcomes of coronary heart disease and stroke and secondary outcomes of hip and other fractures; (2) low fat dietary intervention with primary outcomes of breast cancer and colorectal cancer and a secondary outcome of coronary heart disease; and (3) calcium and vitamin D supplementation with a primary outcome of hip fractures and secondary outcomes of colorectal cancer and combined fractures. A concurrent observational study will provide estimates of health effects of known risk factors and new predictors for disease. Each clinical center will collect data through questionnaires and biological specimens over 8-12 years.